Abstract
Although diabetes mellitus (DM) is recognized as one of the important risk factors for the development of heart diseases, little is known about the impact of DM on cardiac cell-volume regulation. We attempted to assess this point using an animal model. Streptozotocin (STZ, 250 mg/kg body-weight) was injected to adult male mice, and many of the so-treated mice developed Type-I DM in a few days after STZ. The cell-volume regulation and the volume-regulated chloride (Cl−) current (ICl,vol) were examined in single ventricular myocytes obtained from the DM mice, using video-image analysis and the whole-cell voltage-clamp. DM mice showed a loss of body-weight and an increase in blood-glucose level, but there was no change in the heart- to body-weight ratio. Video-image analysis showed that regulatory volume decrease (RVD) was almost lost in myocytes from DM mice, even though myocytes from both age-matched normal and DM mice underwent a similar cell swelling in response to hypotonic challenge. Voltage-clamp study revealed an approximately 50% reduction of the density of ICl,vol in myocytes from DM mice. The density of the basal Cl− current was similar in control and DM mice. Neither the loss of RVD nor the reduction of ICl,vol was observed in myocytes obtained from the mice which had been given STZ only 12 hr before, suggesting that STZ does not directly knock down the ICl,vol channels. Our results indicate that cardiac cellular RVD is attenuated in DM mice, and that the loss of RVD is due at least partly to symptomatic suppression of ICl,vol. [J Physiol Sci. 2007;57 Suppl:S201]
